Methods. We systematically searched PUBMED/MEDLINE and the

Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria. Results. The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ Level), osteoarthritis (1A+ Level), and juvenile idiopathic arthritis (2C+ Level). Pain relief and functional improvement are significant for months up to 1 year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ Level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ Level). It can also be effective for rheumatoid arthritis knee pain (1A+ Level). However, it is only recommended for patients this website with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B +/- Level). Botulinum toxin type A injection is effective in reducing arthritic knee pain (2B+ Level), and so is tropisetron (2B+ Level) and tanezumab (2B+ Level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, Selleck AZD8186 but their long-term safety and efficacy

remains to be determined. Conclusions. We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and BYL719 chemical structure knee surgeries.”
“Cerebral venous thrombosis is an uncommon and diverse entity accounting for less than 1% of strokes. It can present with a variety of clinical symptoms ranging from isolated headaches to deep coma making the clinical diagnosis difficult. We present a rare case of cerebral venous thrombosis secondary to dehydration and inflammatory bowel disease.”
“AimTo determine the adequacy of antenatal calcium intake in Malaysia, and the influencing factors.

MethodsA cross-sectional

study was conducted among postnatal women who delivered in two tertiary hospitals. Data were collected from antenatal cards, hospital documents and diet recall on daily milk and calcium intake during pregnancy. SPSS version 19.0 was used for statistical analyses.

ResultsA total of 150 women were studied. The total daily calcium intake was 83443mg (mean +/- standard error of the mean), but the calcium intake distribution curve was skewed to the right with a median intake of 725mg daily. When calcium intake from milk and calcium supplements was excluded, the daily dietary calcium intake was only 478 +/- 25mg. Even with inclusion of milk and calcium supplements, more than a third (n=55 or 36.7%) of the women consumed less than 600mg calcium in their daily diet.

0 kGy were acceptable under storage for 60 days, compared to 30 days for air-packaged non-irradiated samples.”
“To improve the antifouling characteristics, CCI-779 ic50 polypropylene microporous membranes (PPHFMMs) were surface-modified by the sequential photoinduced graft polymerization of acrylic acid and acrylamide. The grafting density and the grafting chain length, which played

important roles in the antifouling characteristics, were controlled in the first and the second step, respectively. The ATR/FTIR results clearly indicated the successful modification on the membrane surface. The static water contact angle of the modified membrane reduced obviously with the increase of the grafting chain length. The contact angle of the acrylic acid modified membranes was lower than that of the

acrylamide modified membrane with similar grafting chain length. The grafting chain length increased with the increase of UV irradiation time and monomer concentration. The grafting chain length of poly(acrylic acid) (PAAc) was lower than that of the polyacrylamide (PAAm) under the same polymerization conditions. Pure water flux for the modified membranes increased with the increase of grafting chain length, and had maximums. The antifouling GSK2879552 ic50 characteristics of the modified membranes in a submerged membrane-bioreactor (SMBR) were evaluated. The modified membranes showed better filtration performances in the SMBR than the unmodified membrane, and the acrylic acid grafted membrane presented better antifouling characteristics than acrylamide modified membranes. The results demonstrated that the surface carboxyl-containing membranes were better than the surface amido-containing PF-6463922 mw membranes. The results of Pearson correlations demonstrated that the PAAc modified membranes with longer grafting chain length had higher flux recoveries, while the PAAm modified membranes with longer grafting chain length had lower flux recoveries. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115: 2302-2309, 2010″
“Background: The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction

of Plasmodium falciparum transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on Plasmodium stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (Azadirachta indica, Meliaceae) seeds, is a promising candidate, inhibiting Plasmodium exflagellation in vitro at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal (R), an azadirachtin-enriched extract of neem seeds, using the rodent malaria in vivo model Plasmodium berghei/Anopheles stephensi.

Methods: Anopheles stephensi females were offered a blood-meal on P.

The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with an increased frequency of mutations, slow growth and adaptation of the bacteria to the conditions in the lungs, and to antibiotic therapy. Low bacterial metabolic activity and increase of doubling times of the bacterial cells in CF lungs are responsible for some of the tolerance to antibiotics. Conventional resistance

mechanisms, such as chromosomal beta-lactamase, upregulated efflux pumps, beta-catenin assay and mutations of antibiotic target molecules in the bacteria, also contribute to the survival of P. aeruglnosa biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy.”
“Atomic layer deposition was used to deposit amorphous Er-doped Al2O3 films (0.9-6.2 at. % Er) on Si(100). The Er3+ photoluminescence (PL), Er3+ upconversion luminescence, as well as the Si PL and associated surface passivation properties of the films were studied and related to the structural change of the material during

annealing. The PL signals from Er3+ and Si were strongly dependent on the annealing temperature (T = 450-1000 degrees C), but not directly influenced by the transition from an amorphous to a crystalline phase at T > 900 degrees C. For T > 650 degrees C, broad Er3+ PL centered at 1.54 mu m Citarinostat molecular weight (I-4(13/2)) with a full width at half maximum of 55 nm was observed under excitation of 532 nm light. The PL signal reached a maximum for Er Crenigacestat concentrations in the range of 2-3 at. %. Multiple photon upconversion luminescence was detected at 660 nm (F-4(9/2)), 810 nm (I-4(9/2)), and 980 nm (I-4(11/2)), under excitation of 1480 nm light. The optical

activation of Er3+ was related to the removal of quenching impurities, such as OH (3 at. % H present initially) as also indicated by thermal effusion experiments. In contrast to the Er3+ PL signal, the Si luminescence, and consequently the Si surface passivation, decreased for increasing annealing temperatures. This trade-off between surface passivation quality and Er3+ PL can be attributed to an opposite correlation with the decreasing hydrogen content in the films during thermal treatment. (C) 2011 American Institute of Physics. [doi:10.1063/1.3595691]“
“Objective: The aim of this study was to develop a postoperative prognostic nomogram for disease-free survival in patients with renal adenocarcinoma. Materials and Methods: A total of 224 patients with organ-confined or locally advanced renal adenocarcinoma were treated with radical or partial nephrectomy. The variables included in the model were age, histological type, pathological stage, Fuhrman grade and DNA ploidy. Tumor recurrence was defined as any clinical evidence of recurrence.

We searched PUBMED, EM BASE, COCHRANNE, and LILACS databases for studies published until September 9th, 2013, using the keywords “”multiple sclerosis”" “”vitamin D”", and “”clinical trial”". There is no scientific evidence up to the production of this consensus for the use of vitamin

D as monotherapy for MS in clinical practice.”
“Incidence of cancer of unknown primary (CUP) varies globally, and environmental factors are suspected to be related to its development. Immigrant studies offer insights into disease etiology, but no studies have been published on CUP. We investigated CUP risk in immigrants to Sweden to search for etiological learn more clues. The nationwide Swedish Family Cancer Database was used to calculate standardized incidence ratios for CUP in the first-generation immigrants compared with native Swedes from 1958 to 2008. A total of 2340 patients with CUP were identified among immigrants during a follow-up of 23 million person-years compared with

30 507 patients with CUP identified in native Swedes who were followed for 260 million person-years, showing an overall standardized incidence ratio of 0.88 (95% confidence interval: 0.85-0.93). The median age at immigration was 28 years for men and 27 for women. Significantly lower CUP risks, ranging from 0.18 to 0.89, were mainly observed among Finnish, German, and Asian immigrants. The decreased risks click here tended to be lower for women compared with men. Danes of both sexes had an increased risk. The increased or decreased CUP risks observed in this novel study suggested that early life environmental risk factors or genetic factors influence the development of CUP. The risk patterns were modified by sex. The observed differences may give clues about incidence rates in countries of origin for which incidence data are lacking. European Journal of Cancer Prevention 21:10-14 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“A 63-year old man had dysphagia for 4 months and was admitted to our hospital with sudden haematemesis. Computed tomography revealed an aberrant right subclavian artery (ARSA) aneurysm and free air inside the aneurysm. Arterio-oesophageal fistula was diagnosed, and an emergency

operation was performed. Before thoracotomy, a percutaneous transluminal angioplasty (PTA) balloon was inserted from the right brachial artery and selleck screening library placed at the orifice of the ARSA to control bleeding. Through a left thoracotomy, the aorta was excised and the orifice of the ARSA was exposed. There was no sign of infection in the operative field. Bleeding from the ARSA was controlled by balloon occlusion. The proximal portion of the right vertebral artery was ligated and blood backflow from the ARSA stopped. The ARSA was ligated proximal to the aneurysm, and the orifice of the ARSA to the aorta was closed. The infected aneurysm was not resected. The descending aorta was replaced by a rifampin-bonded artificial graft, and omentopexy was performed.

Although there are no specific features on imaging, mixed solid and cystic morphology, fat signal and areas of calcification are helpful in the pre-operative diagnosis. Most of these lesions are diagnosed on histopathological examination after surgery and therefore thorough sampling and serial sectioning are mandatory to identify all components of the teratoma in order to avoid

misdiagnosis.”
“It has been shown that low-level preformed donor-specific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. buy BMS-345541 The relevance of preformed DSAbs in patients receiving alemtuzumab induction see more and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p =

0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibody-mediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive

regime incorporating selleck screening library alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.”
“Study Design. To detect drug concentration levels and metabolite using high-performance liquid chromatography.

Objective. To map concentration levels of three antituberculous drugs and two metabolites in the abnormal osseous tissues around the foci of patients with spinal tuberculosis.

Summary of Background Data. Concentration levels of antituberculous drugs in the focus of spinal tuberculosis has been reported. However, the mapping of drugs distribution in different regions surrounding the foci of tuberculosis vertebrae remains unexplored, as well as the metabolite of the drugs.

Methods. Thirty-eight patients with spinal tuberculosis were assigned into sclerotic group (n = 13) and nonsclerotic group (n = 25) based on computed tomographic (CT) images. All patients received a chemotherapy 10 months with 2HRZE/8H(2)R(2)E(2). All patients received surgery after 4 weeks of chemotherapy. Samples of serum, ilium, and pathologic vertebral tissues, including the foci, sclerotic wall (if applicable), region I of abnormal osseous tissues (within 4 mm), and region II of abnormal osseous tissues (more than 4 mm) from the foci were collected during operation.

We observed an increase of enzyme activity from the green to the red stage of fruits development, suggesting that ONPP activity might be related to the ripening CT99021 of prickly pears. The protein was shown to be resistant to 75 degrees C for 30 min. Other biochemical characteristics were investigated and are reported here. (C) 2010 Elsevier Ltd. All

rights reserved.”
“The objectives of this review are to compare the effectiveness and safety of radiochemotherapy (RTCT) with radiotherapy (RT) alone in locally advanced cervical cancer (LACC).

We comprehensively searched the Cochrane library, Medline, EMBASE, Chinese biomedicine literature database, Chinese scientific full-text database and Chinese journal www.selleckchem.com/products/mrt67307.html full-text database for relevant articles. The computer search was supplemented with a manual search of reference lists for all available review articles. Also reference lists of the included studies were reviewed.

We included 18 randomized trials involving 3,517 patients. Meta-analysis results are as follows: the response rate, 3 and 5-year survival rates were significantly better in patients in the RTCT group than in RT group. As adverse effects, limited

evidence suggests that there was no significant difference between the two groups with regard to rectitis, cystitis, nausea and vomiting. But RTCT group has higher incidence rates than RT group in gastrointestinal, myelosuppression and leucopenia.

The combination of radiotherapy and chemotherapy was more effective for LACC than radiotherapy alone. There was no significant Selleck LY2090314 difference between the RTCT regimen group and RT regimen group with regard to adverse effects.”
“Melamine intoxication

is a present focus in global public health. The problem of renal failure in melamine intoxication is a new topic in nephrology, and the exact mechanism of this scenario needs verification. In this paper, the author reports on energy fluctuation in the formation of melamine cyanurate reaction. The author further implies that this process is a factor leading to acute renal failure in melamine toxicity.”
“This study investigated whether heat-killed Lactobacillus protects host animal against influenza virus infection and stimulates their immunity. Heat-killed Lactobacillus gasseri TMC0356 was orally administered to BALB/c mice for 19 days; the mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and clinical symptoms were monitored. After 6 days, the mice were sacrificed, and pulmonary virus titres were determined. Splenic activation of natural killer (NK) cells and the mRNA expression of cytokines and other immune molecules in the lung and Peyer’s patch (PP) were analysed. Clinical symptom scores of mice orally fed TMC0356 ameliorated significantly (P < 0.01); their pulmonary virus titres decreased significantly compared with those of control mice (P < 0.

TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T wave (Tp-e). Tp-e may therefore provide a readily available, noninvasive assay of drug torsadogenicity. The perioperative period is one of high risk for TdP in children with or at risk of long QT syndromes. Droperidol and ondansetron are two drugs commonly administered perioperatively, for prophylaxis of nausea and vomiting, which

can prolong the QT interval. This study investigated their effects on myocardial repolarization.

Methods:

One hundred and eight ASA1-2 children undergoing elective day-case surgery were randomized to receive droperidol, ondansetron, both or neither. Pre- and post-administration 12-lead electrocardiogram (ECGs) were recorded. QT and Tp-e intervals were measured and compared within and between AZD4547 in vivo groups, for the primary endpoint of a 25 ms change in Tp-e.

Results:

Eighty children completed the AZD6094 cell line study. There were no demographic or baseline ECG differences between groups. QT intervals lengthened by 10-17 ms after allocated

treatments, with no between-group differences. Values remained within normal limits for all groups. Tp-e intervals increased by 0-7 ms, with no between-group differences. There were no instances of dysrhythmia.

Conclusions:

Droperidol and ondansetron, in therapeutic anti-emetic doses, produce equivalent, clinically insignificant QT prolongation and negligible Tp-e prolongation,

suggesting that neither is torsadogenic in healthy children at these doses.”
“Clinical trials have shown the benefits of acetylcholinesterase inhibitors, such as donepezil and galantamine, and an N-methyl-d-aspartate GS-7977 manufacturer receptor antagonist, memantine, in patients with Alzheimer’s disease (AD). However, little is known regarding the effects of switching from donepezil 5 mg/day to galantamine 16 or 24 mg/day, or regarding the effects of adding memantine to established therapy compared with increasing the dose of donepezil. This report discusses two studies conducted to evaluate treatment with galantamine and memantine with respect to cognitive benefits and caregiver evaluations in patients with AD receiving donepezil 5 mg/day for more than 6 months. Patients with mild or moderate AD (scores 10-22 on the Mini-Mental State Examination) were enrolled in the Galantamine Switch study and switched to galantamine (maximum doses 16 mg versus 24 mg). Patients with moderate to severe AD (MiniMental State Examination scores 3-14) were enrolled in the Donepezil Increase versus Additional Memantine study and either had their donepezil dose increased to 10 mg/day or memantine 20 mg/day added to their existing donepezil dose.

These radiographs were then analyzed with image-processing software to measure www.selleckchem.com/products/nocodazole.html the peri-implant crestal bone change during the healing phase (4 months after implant placement) and at loading phases 1 and 2 (3 and

6 months after occlusal loading, respectively). A generalized estimating equation method was employed for statistical analysis. The amount of peri-implant crestal bone change differed significantly among all time-phase pairs for all 3 types of implant-abutment connection, being greater in the healing phase than in loading phase 1 or 2. However, the peri-implant crestal bone change did not differ significantly among the 3 types of implant-abutment connections during the healing phase,

loading phase 1, or loading phase 2. This retrospective clinical study reveals that the design of the implant-abutment connection appears to have no significant impact on short-term peri-implant crestal bone change.”
“Context: The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals Nutlin-3 ic50 and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects.

Objectives: To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing find more considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U. S Food

and Drug Administration and the European Union regulatory agencies).

Materials and methods: We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.”
“OBJECTIVE: To estimate whether the use of regional anesthesia is associated with increased success of external cephalic version.

DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trial registries.

METHODS OF STUDY SELECTION: Electronic databases were searched from 1966 through April 2011 for published, randomized controlled trials in the English language comparing regional anesthesia with no regional anesthesia for external cephalic version. The primary outcome was external cephalic version success. Secondary outcomes included cesarean delivery, maternal discomfort, and adverse events.

Community and hospital acquired S. aureus isolates (n = 202) were characterized using staphylococcal cassette chromosome mec (SCCmec) typing, pulse field gel electrophoresis (PFGE) analysis, spa typing and minimal inhibitory concentration (MIC) determination. The prevalence of the Panton-Valentine leukocidine (pvl) and several antibiotic resistance genes among the isolates were also detected by PCR. All of the S. aureus isolates were

susceptible to vancomycin, daptomycin and linezolid. Three hospital Ricolinostat chemical structure isolates were resistant to teicoplanin while 14 showed intermediate resistance to teicoplanin. The resistance patterns of community-acquired MRSA (CA-MRSA) isolates to other antimicrobials were similar to those of hospital-acquired MRSA (HA-MRSA) isolates except for clindamycin and gentamicin. There was excellent correlation between phenotypes and genotypes in the determination of S. aureus resistance to erythromycin,

gentamicin, and tetracycline. The SCCmec type II and SCCmec type IV were the predominant types detected in hospital and community isolates, respectively. The most frequently encountered spa types were t002 and t030 both in HA-and CA-MRSA isolates. Pulsotype A was the most predominant pulsotype identified among the isolates tested, followed by pulsotype B. Seventy-two hospital isolates (19 HA-MRSA and 53 HA-MSSA) and 10 CA-MRSA were positive for the pvl gene. This study shows that the combination of susceptibility testing and various molecular methods has provided useful information on the antibiotic BMN 673 research buy resistance and molecular diversity of S. aureus in a specific region of China. The high proportion of pvl positive MSSA and MRSA isolates observed in this study indicates that adequate measures are needed to curtail the spread of those MRSA and MSSA clones prevailing both in hospital and the community. (C) 2013 Elsevier Editora Ltda. All rights reserved.”
“Background and Navitoclax Objectives: Enterococci are part of the normal flora of the gastrointestinal tract. They can

cause -enteric peritonitis, which is a serious complication of peritoneal dialysis (PD). However, the clinical course and outcome of PD-related Enterococcus peritonitis remains unclear.

Methods: We reviewed all Enterococcus peritonitis episodes occurring in our dialysis unit from 1995 to 2009.

Results: During the study period, 1421 episodes of peritonitis were recorded. Of 29 episodes (2.0%) that were attributable to single-organism Enterococcus, 12 episodes were caused by E. faecalis; 9, by E. faecium; and the remaining 8, by other Enterococcus species. The overall rate of ampicillin resistance was 41.4%. Recent use of antibiotics was associated with the development of ampicillin-resistant Enterococcus (ARE) peritonitis (hazard ratio: 12.53; p = 0.04). The primary response rate of Enterococcus peritonitis was significantly higher than that of Escherichia coli peritonitis (89.7% vs. 69.9%, p = 0.

This validated Motivation Questionnaire is an instrument to test the impact of motivation upon cure, in PFMT.”
“The atomic structure, buy CX-6258 adhesion energy, and bonding nature of the YBa2Cu3O7(001)/SrTiO3 (00 1) interface are systematically investigated from first principles. A total of 48 candidate interface geometries, which involve two SrTiO3 terminations, six YBa2Cu3O7 terminations, and four highly symmetric stacking sequences. were considered. Although the SrTiO3 substrate has a negligible effect on the atomic structure of optimal TiO2-terminated interface, its electronic influence is significant: the electronic states of interfacial O of YBa2Cu3O7 resemble

those of O in bulk SrTiO3 rather than bulk YBa2Cu3O7-Consequently, the interfacial O of YBa2Cu3O7 can be reasonably regarded as a natural extension of substrate layer across the interface. However, the effect of substrate on the optimal SrO-terminated interface is twofold characterized atomically by straightening the originally zigzag interfacial YBa2Cu3O7 layer and electronically by altering noticeably the density of states projected oil this layer. In addition, the substrate is found to affect the interface chemistry via tuning effectively the first monolayer of the YBa2Cu3O7 film. The preferred geometries (i.e., having the largest adhesion energy) selleck chemical are those

that maintain the substrate perovskite stacking across the interface. By applying several methods of analysis, we thoroughly characterized electronic structure and determined that interfacial bonding is mainly ionic, yet maintains a small degree of covalency. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3257264]“
“Objective People with cancer may experience distress related to diagnoses, disease-related symptoms, and treatment side effects. Assessment of cancer-related needs can facilitate timely triage and intervention and contribute to individualized comprehensive cancer care. This study assessed the internal consistency, testretest reliability and construct validity of the Cancer Needs Distress Inventory (CaNDI), a self-report, needs-based measure

of cancer-related distress. Methods A sample of 100 patients (27% male) with various cancer diagnoses completed the CaNDI, Hospital Anxiety and Depression Scale, Brief Symptom I-BET-762 chemical structure Inventory, Functional Assessment of Cancer Therapy-General, and the Paulhus Deception Scales. Results The CaNDI total and depressive and anxiety subscale scores all demonstrated excellent testretest reliability and moderate to high correlations with other measures of these constructs. The instrument was minimally confounded by social desirability and provided high sensitivity and specificity in detecting depression and anxiety. Conclusions Initial results suggest that the CaNDI has strong psychometric properties and may be a useful addition to cancer patient needs assessment, research and care. Copyright (c) 2011 John Wiley & Sons, Ltd.